Evaluation of analgesic effect, joint function recovery and safety of meloxicam in knee osteoarthritis patients who receive total knee arthroplasty: A randomized, controlled, double-blind study.

ABSTRACT: Meloxicam is commonly administrated to control postoperative pain in orthopedic surgery, while its efficacy in total knee arthroplasty (TKA) is not clear. Therefore, this study aimed to explore the postoperative analgesic effect and tolerance of meloxicam in knee osteoarthritis (OA) patients undergoing TKA.Totally, 128 knee OA patients scheduled for TKA were enrolled in this randomized, controlled, double-blind study, then randomized into meloxicam group (N = 65) and control group (N = 63) as 1:1 ratio. Patients took meloxicam or placebo from 4 hours (h) to 72 h after TKA. Patients were followed up at 6 h, 12 h, day (D)1, D2, D3, D7, month (M)1, and M3.Pain visual analog scale score at rest was decreased in meloxicam group at 12 h, D1 and D3 compared to control group; pain visual analog scale score at flexion was reduced in meloxicam group at 6 h, 12 h, D1, D2, and D3 compared to control group. Additional and total consumption of patient-controlled analgesia were both attenuated in meloxicam group compared to control group. Furthermore, patient satisfaction score was higher on D1, D2, D3 in meloxicam group compared to control group. However, no difference of hospital for special surgery knee score score at M1 or M3 was found between the 2 groups. Moreover, the occurrence of adverse events was similar between the 2 groups.Meloxicam displays good effect on controlling postoperative pain and improving patient satisfaction, while does not affect long-term knee function recovery or safety profile in knee OA patients undergoing TKA.

Ibuprofen Better than Acetaminophen for Reducing Fever, Pain in Young Children.

According to this study: In children younger than age two, treatment with ibuprofen was associated with reduced fever and less pain within the first 24 hours compared with acetaminophen.The incidence of adverse events was low with both treatments.

Fever response to ibuprofen in viral and bacterial childhood infections.

OBJECTIVE: to compare the antipyretic effects of ibuprofen in febrile children with serious bacterial infections (SBI), and children with a presumed viral infection. METHODS: A prospective cross- sectional study was conducted in a pediatric Emergency department between October 2018 and March 2020 for children aged 3 months to 4 years with a rectal temperature ≥ 38.5 °C. Patients received 10 mg/kg of ibuprofen oral suspension. Rectal temperature was measured 60 and 120 min after administration. Laboratory and imaging evaluations were performed for each study participant in order to identify serious bacterial infection. RESULTS: Ninety patients were included, of which 18 were diagnosed with serious bacterial infections. There was no significant difference in age, fever at presentation and duration of fever between the groups. No significant difference was noted in body temperature reduction at 60 and 120 min after ibuprofen administration (1.09 ± 0.75 °C vs 0.89 ± 0.58 °C, mean difference -0.12 °C, 95% CI -0.54-0.15 °C; 1.85 ± 0.53 °C vs 1.78 ± 0.83 °C, mean difference - 0.07 °C, 95% CI -0.49-0.36 °C, in the SBI and non-SBI groups respectively). CONCLUSION: Fever response to Ibuprofen administration is not indicative of serious bacterial infections in children under 4 years of age. Larger prospective studies are required to define whether the lack of response to Ibuprofen has any impact on the management of febrile children.

Comparison of Acetaminophen (Paracetamol) With Ibuprofen for Treatment of Fever or Pain in Children Younger Than 2 Years: A Systematic Review and Meta-analysis.

Importance: Acetaminophen (paracetamol) and ibuprofen are the most widely prescribed and available over-the-counter medications for management of fever and pain in children. Despite the common use of these medications, treatment recommendations for young children remain divergent. Objective: To compare acetaminophen with ibuprofen for the short-term treatment of fever or pain in children younger than 2 years. Data Sources: Systematic search of the databases MEDLINE, Embase, CINAHL, and the Cochrane Central Register of Controlled Trials and the trial registers ClinicalTrials.gov and the Australian New Zealand Clinical Trials Registry from inception to March 2019, with no language limits. Study Selection: Studies of any design that included children younger than 2 years and directly compared acetaminophen with ibuprofen, reporting antipyretic, analgesic, and/or safety outcomes were considered. There were no limits on length of follow-up. Data Extraction and Synthesis: Following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guideline, 2 authors independently extracted data and assessed quality. Data were pooled using a fixed-effects method if I2 was less than 50% and using a random-effects method if I2 was 50% or greater. Main Outcomes and Measures: The primary outcomes were fever or pain within 4 hours of treatment onset. Safety outcomes included serious adverse events, kidney impairment, gastrointestinal bleeding, hepatotoxicity, severe soft tissue infection, empyema, and asthma and/or wheeze. Results: Overall, 19 studies (11 randomized; 8 nonrandomized) of 241 138 participants from 7 countries and various health care settings (hospital-based and community-based) were included. Compared with acetaminophen, ibuprofen resulted in reduced temperature at less than 4 hours (4 studies with 435 participants; standardized mean difference [SMD], 0.38; 95% CI, 0.08-0.67; P = .01; I2 = 49%; moderate quality evidence) and at 4 to 24 hours (5 studies with 879 participants; SMD, 0.24; 95% CI, 0.03-0.45; P = .03; I2 = 57%; moderate-quality evidence) and less pain at 4 to 24 hours (2 studies with 535 participants; SMD, 0.20; 95% CI, 0.03-0.37; P = .02; I2 = 25%; moderate-quality evidence). Adverse events were uncommon. Acetaminophen and ibuprofen appeared to have similar serious adverse event profiles (7 studies with 27 932 participants; ibuprofen vs aceteminophen: odds ratio, 1.08; 95% CI, 0.87-1.33; P = .50, I2 = 0%; moderate-quality evidence). Conclusions and Relevance: In this study, use of ibuprofen vs acetaminophen for the treatment of fever or pain in children younger than 2 years was associated with reduced temperature and less pain within the first 24 hours of treatment, with equivalent safety.

Efficacy and Safety of Naproxen for Acute Pain.

Acute pain often is treated with over-the-counter (OTC) therapeutics, including non-steroidal anti-inflammatory drugs (NSAIDs). However, not all NSAIDs are equally effective for treating different types of acute pain. In this article, we review the data supporting the use of OTC naproxen to effectively treat a variety of types of acute pain, including dysmenorrhea, headache, and dental pain, as well as review adverse effects. This information can be used to provide appropriate treatment for patients experiencing acute pain and help prevent progression to chronic pain.

2020 American College of Rheumatology Guideline for the Management of Gout.

OBJECTIVE: To provide guidance for the management of gout, including indications for and optimal use of urate-lowering therapy (ULT), treatment of gout flares, and lifestyle and other medication recommendations. METHODS: Fifty-seven population, intervention, comparator, and outcomes questions were developed, followed by a systematic literature review, including network meta-analyses with ratings of the available evidence according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology, and patient input. A group consensus process was used to compose the final recommendations and grade their strength as strong or conditional. RESULTS: Forty-two recommendations (including 16 strong recommendations) were generated. Strong recommendations included initiation of ULT for all patients with tophaceous gout, radiographic damage due to gout, or frequent gout flares; allopurinol as the preferred first-line ULT, including for those with moderate-to-severe chronic kidney disease (CKD; stage >3); using a low starting dose of allopurinol (≤100 mg/day, and lower in CKD) or febuxostat (<40 mg/day); and a treat-to-target management strategy with ULT dose titration guided by serial serum urate (SU) measurements, with an SU target of <6 mg/dl. When initiating ULT, concomitant antiinflammatory prophylaxis therapy for a duration of at least 3-6 months was strongly recommended. For management of gout flares, colchicine, nonsteroidal antiinflammatory drugs, or glucocorticoids (oral, intraarticular, or intramuscular) were strongly recommended. CONCLUSION: Using GRADE methodology and informed by a consensus process based on evidence from the current literature and patient preferences, this guideline provides direction for clinicians and patients making decisions on the management of gout.

Comparison of kidney-tonifying and blood-activating medicinal herbs vs NSAIDs in patients with knee osteoarthritis: A protocol for a systematic review and meta-analysis.

BACKGROUND: Knee osteoarthritis (KOA) is one of the most common chronic muscular diseases in old people. In recent years, people are more and more interested in the use of Chinese herbal medicine (CHM) in the treatment of KOA, such as kidney-tonifying and blood-activating medicinal herbs (KTBAMs) in the treatment of KOA. Many studies have confirmed that KTBAMs are effective in the treatment of KOA. However, it is still unknown whether KTBAMs and NSAIDs are more effective in the treatment of KOA. Therefore, we evaluated the efficacy and safety of KTBAMs and NSAIDs in the treatment of KOA. METHODS: Randomized controlled trials (RCTs) from online databases including PubMed, Embase, the Cochrane Library, China National Knowledge Infrastructure, Chinese Scientific Journal Database, Wanfang Data, and Chinese Biomedical Literature Database that compared the efficacy of KTBAMs and NSAIDs in the treatment of KOA were retrieved. The main outcomes included the evaluation of functional outcomes, pain and adverse effects. The Cochrane risk of bias (ROB) tool was used to assess methodological quality. RESULTS: The literature will provide a high-quality analysis of the current evidence supporting KTBAMs for KOA based on various comprehensive assessments including the total effective rate, visual analog scale scores, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Lequence scores, Knee Society Scale (KSS) scores, and adverse effects. CONCLUSION: This proposed systematic review will provide up-to-date evidence to assess the effect of KTBAMs in the treatment for patients with KOA. RESEARCH REGISTRY REGISTRATION NUMBER: : reviewregistry 783.

Batch-to-Batch Consistency of SB4 and SB2, Etanercept and Infliximab Biosimilars.

BACKGROUND: Biosimilars must meet stringent regulatory requirements, both at the time of authorization and during their lifecycle. Yet it has been suggested that divergence in quality attributes over time may lead to clinically meaningful differences between two versions of a biologic. Therefore, this study investigated the batch-to-batch consistency across a range of parameters for released batches of the etanercept biosimilar (SB4) and infliximab biosimilar (SB2). METHODS: SB4 (Benepali®) and SB2 (Flixabi®) were both developed by Samsung Bioepis and are manufactured in Europe by Biogen at their facility in Hillerød, Denmark. A total of 120 batches of SB4 and 25 batches of SB2 were assessed for consistency and compliance with specified release parameters, including purity, post-translational glycosylation (SB4 only), protein concentration, and biological activity. RESULTS: The protein concentration, purity, tumor necrosis factor-α (TNF-α) binding, and TNF-α neutralization of all batches of SB4 and SB2 were within the strict specification limits set by regulatory agencies, as was the total sialic acid (TSA) content of all batches of SB4. CONCLUSIONS: Quality attributes of SB4 and SB2 batches showed little variation and were consistently within the rigorous specifications defined by regulatory agencies.

Preparation of celecoxib tablet by hot melt extrusion technology and application of process analysis technology to discriminate solubilization effect.

The aim of this study was to prepare various types of solid dispersions (SDs) by the hot-melt extrusion technique. Next, process analytical technology (PAT) such as Fourier transform-infrared (FT-IR) and Raman and near infrared (NIR) spectroscopy were applied to determine the solubilization effect. The SDs and its tablets were prepared. Differential scanning calorimetry (DSC), X-ray diffraction (XRD), and scanning electron microscopy (SEM) were performed to determine the morphological and crystalline characteristics of the SDs. Additionally, PAT analyses were performed to identify the solubilization of the celecoxib. Dissolution testing was performed using the paddle method indicated in the US Pharmacopeia Apparatus II. Based on SEM, DSC, and XRD analysis, all SDs changed successfully from the crystalline to the amorphous form. However, FT-IR, Raman, and NIR analysis used in PAT showed that SDs were divided into two groups. New peaks formed as the amount of drug loading increased to >50% in the SD and the dissolution rates were lower than those of the marketed drug. Drug loading levels of ≤50% showed no new peak and exhibited strong solubilization effects. PAT tools can be used to discriminate between extrudates with poor (<50% drug release after 120 min) and desirable (>75% drug release after 120 min) dissolution performance.

The effect of critical process parameters of the high pressure homogenization technique on the critical quality attributes of flurbiprofen nanosuspensions.

Flurbiprofen (FB) is an effective nonsteroidal anti-inflammatory and BCS class II drug and its poor solubility plays a critical role in limiting its bioavailability. Nanosuspensions can be defined as nanosized colloidal dispersions of drug particles stabilized with stabilizers. The solubility of poor soluble drugs can be increased thanks to their small size and large surface area. The aim of this study is to optimize FB nanosuspensions. The formulations were stabilized with Plantacare 2000® as a surfactant using a combination of High Speed Homogenization (HSH) and High Pressure Homogenization techniques (HPH). We also investigated the effects of the critical process parameters (CPPs) of these techniques (homogenization speed & time for HSH and homogenization pressure & cycle for HPH) on three critical quality attributes of nanosuspensions, being the particle size (PS), polydispersity index (PDI) and zeta potential (ZP). After the optimization of HSH, the macrosuspension was transferred to a high pressure homogenizer. After producing FB nanosuspensions by the HPH technique, seven processes which comprise different homogenization pressures, or combinations and different cycles, were applied. Due to the combination of HSH and HPH techniques and the optimization of CPPs, an optimum formulation for a dermal application was found using a 33 full factorial design with these process parameters, and characterization studies were also performed.

Pharmacological control of inflammation in wound healing.

Wound inflammation is a rapid and highly orchestrated process that significantly impacts the wound healing cascade. Consequent to injury, a series of events set off that include inflammatory, proliferation and maturation phases leading to wound closure and restoration of normal skin integrity. Stimuli causing stress to host immune system or induce inflammatory response include tissue damage and pathogenic microbial infection.Several evidences points towards the positive role of inflammation as it essential to fight against the attack of invading pathogens and to remove dead tissues from the site of injury. Besides its positive role, prolonged inflammation is injurious and may result in deregulated stages of the wound healing which may lead to excessive scarring. Achieving balance in inflammatory cascade is one of the challenging tasks for development of a wound healing drug. This review mainly focuses on the pharmacological control of inflammation by agents which critically balance the inflammatory cascade. However, none of the agent is available in the healthcare market which exclusively plays a role in wound repair. In this review we shall explore different factors or agents affecting inflammation in wound healing. This information might be helpful in designing and development new process, technologies or drugs for better management of wound care. In addition, understanding the effect of inflammation on the outcome of the healing process will serve as a significant milestone in the area of pathological tissue repair.

Self-Reported Pain Interference and Analgesic Characteristics in Rural Older Adults.

BACKGROUND: Pain impacts the lives of millions of community-dwelling older adults. An important characteristic of pain is "pain interference" which describes the influence of pain on function. A description of pain interference is limited in rural settings where the number of older adults is expected to increase, and health disparities exist. AIMS: The purpose of this study was to describe pain interference and analgesic medication use, highlighting those that may be potentially inappropriate in a sample of rural community-dwelling older adults. DESIGN: This secondary analysis was from a cross sectional study. SAMPLE AND SETTINGS: Data were analyzed from a sample of 138 rural community-dwelling older adults. METHODS: Statistical analyses were performed on demographics, health characteristics, pain interference, and potentially inappropriate analgesic medication data. RESULTS: Pain interference with work activity was reported by 76% of older adults overall, with 23% reporting moderate and 4% extreme interference, and 41% reported sleep difficulty due to pain. Higher pain interference was significantly associated with higher body mass index, more health providers, and the daily use of non-steroidal anti-inflammatory drugs (NSAIDs). Older women experienced more sleep difficulties due to pain. Over-the-counter analgesics were used most frequently by rural older adults to manage pain. Of most risk was the daily use of NSAIDs, in which only 30% used medications to protect the gastrointestinal system. CONCLUSIONS: Older adults in rural settings experience pain interference and participate in independent-medicating behaviors that may impact safety.

ED treatment of migraine patients has changed.

STUDY OBJECTIVES: Numerous studies have shown benefits of nonnarcotic treatments for emergency department (ED) migraine patients. Our goal was to determine if ED treatment of migraine patients and the rate of return within 72 h have changed. METHODS: Design: Multi-hospital retrospective cohort. POPULATION: Consecutive ED patients from 1-1-1999 to 9-31-2014. PROTOCOL: For determining treatments, we examined charts at the beginning (1999-2000) and end (2014) of the time period. We combined similar medications into the following groups: parenteral narcotics, oral narcotics, antihistamines and dopamine receptor antagonists prochlorperazine/metoclopramide (DRA). We calculated the percent of migraine patients given each treatment in each time period. We identified those who returned to the same ED within 72 h, and calculated the difference in annual return rates between 1999-2000 and 2014. RESULTS: Of the 2,824,710 total visits, 8046 (0.28%) were for migraine. We reviewed 290 charts (147 in 1999-2000 and 143 in 2014) to determine migraine treatments. The use of IV fluids, DRA, ketorolac and dexamethasone increased from 1999-2000 to 2014, whereas narcotic use and discharge prescriptions for narcotics decreased. Of the 8046 migraine patients, 624 (8%) returned within 72 h. The return rate decreased from 1999-2000 to 2014 from 12% to 4% (difference = 8%, 95% CI 5%-11%). CONCLUSION: For ED migraine patients, the use of IV fluids, DRA, ketorolac and dexamethasone increased whereas the use of narcotics and discharge prescriptions for narcotics decreased. The return rates for migraines decreased. We speculate that the increased use of non-narcotic medications contributed to this decrease.

2018 update of the EULAR recommendations for the management of hand osteoarthritis.

Since publication of the European League Against Rheumatism (EULAR) recommendations for management of hand osteoarthritis (OA) in 2007 new evidence has emerged. The aim was to update these recommendations. EULAR standardised operating procedures were followed. A systematic literature review was performed, collecting the evidence regarding all non-pharmacological, pharmacological and surgical treatment options for hand OA published to date. Based on the evidence and expert opinion from an international task force of 19 physicians, healthcare professionals and patients from 10 European countries formulated overarching principles and recommendations. Level of evidence, grade of recommendation and level of agreement were allocated to each statement. Five overarching principles and 10 recommendations were agreed on. The overarching principles cover treatment goals, information provision, individualisation of treatment, shared decision-making and the need to consider multidisciplinary and multimodal (non-pharmacological, pharmacological, surgical) treatment approaches. Recommendations 1-3 cover different non-pharmacological treatment options (education, assistive devices, exercises and orthoses). Recommendations 4-8 describe the role of different pharmacological treatments, including topical treatments (preferred over systemic treatments, topical non-steroidal anti-inflammatory drugs (NSAIDs) being first-line choice), oral analgesics (particularly NSAIDs to be considered for symptom relief for a limited duration), chondroitin sulfate (for symptom relief), intra-articular glucocorticoids (generally not recommended, consider for painful interphalangeal OA) and conventional/biological disease-modifying antirheumatic drugs (discouraged). Considerations for surgery are described in recommendation 9. The last recommendation relates to follow-up. The presented EULAR recommendations provide up-to-date guidance on the management of hand OA, based on expert opinion and research evidence.

Comparison the analgesic effect of magnesium sulphate and Ketorolac in the treatment of renal colic patients: Double-blind clinical trial study.

BACKGROUND: Ureter muscles contraction movements caused pain in renal colic. Magnesium sulphate could influence the pain by reducing acetylcholine in the nerve terminals. We have aimed to evaluate the analgesic effects of magnesium sulphate on acute renal colic pain. METHOD: In this double-blind clinical trial study, the patients with renal colic pain were randomly divided into 2 groups; Group I received an intravenous infusion of 30 mg of Ketorolac and normal saline as placebo, Group II 50 mg/kg magnesium sulphate 50%/100 ml normal plus 30 mg of Ketorolac. The pain severity of patients was assessed using the visual analog scale (VAS) at baseline, and 15 and 30 min after intervention. RESULTS: Baseline pain score and demographic characteristics did not significantly different between the groups. After 30 min the pain score significantly reduced in both groups. While, at 15 and 30 min, mean pain score did not show statistically significant differences. CONCLUSION: Our findings indicated that Magnesium sulphate did not influence renal colic pain relief.

Dexibuprofen: Statistical assessment of drug release kinetics and investigative quality perspective.

Healthcare professionals including physicians and pharmacists have been trying since long to come across and work out regarding the issue of generic alternatives, which is highly affected by factors like therapeutic efficacy, cost effectiveness, aesthetic and elegant appearance and implementation of packaging number over the drug product. However, the community pharmacist professionals are also facing difficulty in making decision regarding selection and dispensing the most efficacious brand to the patients. In this regard, the initiation of recent approaches for the development of amenable drug products has led to evolve the concept of generating new avenues for achieving higher patient compliance. Hence, the objective of this study was to evaluate the quality attributes and make comparisons regarding different brands of Dexibuprofen available in market of Karachi, Pakistan. The study is based on evaluation of physical chemical parameters of five different brands. Moreover, a comparative dissolution profile of selected brands of Dexibuprofen was also performed by applying numerous approaches. DEX-1was selected as reference while DEX-2- DEX-5 was selected as test brands. Results of all the selected brands met all the compendial requirements. Interpretation of the entire aforementioned test was evaluated using model independent, model- dependent and one - way ANOVA. The work presented in this study has been designed to provide quality standard products easily accessible in Pakistani market.

Safety of nonsteroidal anti-inflammatory drugs in copperhead snakebite patients.

Introduction: Current management guidelines for pit viper envenomations recommend against the use of nonsteroidal anti-inflammatory drugs (NSAIDs) for pain control due to concern for platelet dysfunction and resulting coagulopathy. However, prior research suggests that copperhead snakes generally do not cause coagulopathy and they are responsible for most of the venomous snakebites in the USA. Thus, we compared the occurrences of clinically apparent bleeding and most abnormal laboratory values of coagulation between copperhead envenomation patients who received NSAIDs and those who did not. Methods: We conducted a retrospective chart review of patients who presented to our adult and pediatrics emergency department with copperhead snakebites. We recorded patient demographics, snake type, any NSAIDs given, any opioid analgesics given, any documented bleeding, and most abnormal laboratory values of coagulation. Results: There was no significant difference in most abnormal PTT, fibrinogen, platelet count, and serum creatinine values between copperhead snakebite patients who received NSAIDs and those who did not. Mean INR was lower (p = .011) and hematocrit was higher (p = .018) for NSAID-treated patients than for patients treated without NSAIDs. Three patients demonstrated clinically apparent bleeding; two had epistaxis reported at an outside hospital but received NSAIDs without further bleeding at our hospital. The third had 3 + blood on a urinalysis that was attributed to a urinary tract infection and also received NSAIDs without any other bleeding. Conclusions: There were no bleeding outcomes attributable to NSAID usage among copperhead snakebite patients. The use of NSAIDs in managing pain and inflammation in identified copperhead snakebite patients appears safe.

Effect of Extra Virgin Olive Oil and Table Olives on the ImmuneInflammatory Responses: Potential Clinical Applications.

BACKGROUND AND OBJECTIVE: Extra virgin olive oil (EVOO) is the common element among the Mediterranean countries. It can be considered a nutraceutical and functional food, thanks to its bioactive compounds. It can act and modulate different processes linked to ageing and age-related diseases related to a common chronic low grade inflammation. Depending on the cultivar, the growth conditions, the period of harvesting, the productive process and time of product storage, EVOO could contain different amount of vegetal components. Of course, the same is for table olives. METHODS: The aim of our review is to summarize the effects of EVOO and table olives on the immunemediated inflammatory response, focusing our attention on human studies. RESULTS: Our report highlights the effect of specific molecules obtained from EVOO on the modulation of specific cytokines and anti-oxidants suggesting the importance of the daily consumption of both EVOO and table olives in the context of a Mediterranean dietary pattern. In addition, the different action on immune-inflammatory biomarkers, are depending on the olive tree cultivar. CONCLUSION: Thanks to their bioactive compounds, EVOO and table olive can be considered as nutraceutical and functional foods. The beneficial effects analysed in this review will help to understand the potential application of specific olive components as therapeutic adjuvant, supplements or drugs.

Extra Virgin Olive Oil and Cardiovascular Diseases: Benefits for Human Health.

BACKGROUND AND OBJECTIVE: The cardioprotective properties of Mediterranean Diet were demonstrated for the first time from the Seven Country Study. In the last few decades, numerous epidemiological studies, as well as intervention trial, confirmed this observation, pointing out the close relationship between the Mediterranean diet and cardiovascular diseases. In this context, extra virgin olive oil (EVOO), the most representative component of this diet, seems to be relevant in lowering the incidence of cardiovascular events, including myocardial infarction and stroke. From a chemical point of view, 98-99% of the total weight of EVOO is represented by fatty acids, especially monounsaturated fatty acids such as oleic acid. Tocopherols, polyphenols and other minor constituents represent the remaining 1-2%. All these components may potentially contribute to "health maintenance" with their beneficial effects by EVOOO. METHODS: Studies that examined the effect of EVOO supplementation in healthy subjects and in individuals at cardiovascular risk were included. CONCLUSION: The studies analyzed demonstrated the role of EVOO as anti-inflammatory, antioxidant and vasodilatory nutrient that may contribute to lower the atherosclerotic burden.